title: Assessment of absorption potential of poorly water-soluble drugs by using the dissolution/permeation system.
abstract: This study aims to assess the absorption potential of oral absorption of poorly water-soluble drugs by using the dissolution/permeation system (D/P system). The D/P system can be used to perform analysis of drug permeation under dissolution process and can predict the fraction of absorbed dose in humans. When celecoxib at 1/100 of a clinical dose was applied to the D/P system, percentage of dose dissolved and permeated significantly decreased with an increase in the applied amount, resulting in the oral absorption being predicted to be 22-55%. Whereas similar dissolution and permeation profiles of montelukast sodium were observed, estimated absorption (69-85%) was slightly affected. Zafirlukast absorption (33-36%) was not significantly affected by the dose, although zafirlukast did not show complete dissolution. The relationship between clinical dose and predicted oral absorption of drugs corresponded well to clinical observations. The limiting step of the oral absorption of celecoxib and montelukast sodium was solubility, while that of zafirlukast was dissolution rate. However, due to high permeability of montelukast, oral absorption was not affected by dose. Therefore, the D/P system is a useful tool to assess the absorption potential of poorly water-soluble drugs for oral use.
authors.affiliation: Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan. Electronic address: makoto@pharm.setsunan.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kataoka
authors.forename: Koji
authors.initials: K
authors.lastname: Yano
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Hamatsu
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Masaoka
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakuma
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D000042:Absorption; D000085:Acetates / Q000737:chemistry* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D018938:Caco-2 Cells; D000068579:Celecoxib; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003521:Cyclopropanes; D006801:Humans; D007211:Indoles; D007408:Intestinal Absorption; D008297:Male; D010539:Permeability; D048448:Phenylcarbamates; D011720:Pyrazoles / Q000737:chemistry* / Q000493:pharmacokinetics; D011804:Quinolines / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013440:Sulfides; D013449:Sulfonamides / Q000737:chemistry* / Q000493:pharmacokinetics; D013678:Technology, Pharmaceutical / Q000379:methods*; D014105:Tosyl Compounds / Q000737:chemistry; D014867:Water / Q000737:chemistry*
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D007211:Indoles; D048448:Phenylcarbamates; D011720:Pyrazoles; D011804:Quinolines; D013440:Sulfides; D013449:Sulfonamides; D014105:Tosyl Compounds; D014867:Water; D000068579:Celecoxib; C093875:montelukast; C062735:zafirlukast
keywords: Dissolution; Maximum absorbable dose; Poorly water-soluble drug; Rate-limiting step; Solubility